Metabolomics Reveals Early Changes in Metabolic Pathways for Alzheimer’s Disease

Eugenia Trushina, Ph.D. Mayo Clinic NIEHS Grant R01ES020715

With funding from the NIEHS, researchers found changes in the metabolic pathways of Alzheimer’s patients that were detectable in blood plasma. The findings suggest that it might be possible to identify plasma biomarkers for early Alzheimer’s disease diagnosis, monitoring disease progression, and evaluating therapeutic approaches.

The researchers used a non-targeted metabolomics approach based on liquid chromatography/mass spectrometry to analyze cerebrospinal fluid and plasma samples from 45 people in the Mayo Clinic Study on Aging and Mayo Clinic Alzheimer's Disease Center. The study participants included 15 people with no cognitive decline, 15 with mild cognitive impairment, and 15 with Alzheimer's disease.

In total, the investigators found 342 plasma and 351 cerebrospinal fluid significantly altered metabolites. When looking at differences between the Alzheimer’s disease and cognitively normal groups, they found altered cholesterol and sphingolipids transport in both cerebrospinal fluid and plasma. Patients with mild cognitive impairment and Alzheimer’s disease showed significant impairment in energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis pathways. As disease severity increased, so did the number of affected pathways for both fluids. Importantly, the changes observed in plasma accurately reflected the changes in cerebrospinal fluid, showing that the biomarkers in the plasma reflected the brain differences of the study participants. The researchers say that additional research using targeted metabolomics could identify specific panels of biomarkers.